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Reviewed, UniProtKB/Swiss-Prot P58397 (ATS12_HUMAN)

Last modified November 4, 2008. Version 77. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 12
      Short name=ADAMTS-12
      Short name=ADAM-TS 12
      Short name=ADAM-TS12
    EC=3.4.24.-
Gene names
Name: ADAMTS12
ORF Names: UNQ1918/PRO4389
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length1593 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subcellular location

Secreted › extracellular space › extracellular matrixBy similarity.

Tissue specificity

Expressed exclusively in fetal lung. Is widely expressed in gastric carcinomas and in cancer cells of diverse origin.

Domain

The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix By similarity.

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Post-translational modification

The precursor is cleaved by a furin endopeptidase.

Subjected to an intracellular maturation process yielding a 120 kDa N-terminal fragment containing the metalloproteinase, disintegrin, one TSP type-1 and the Cys-rich domains and a 83 kDa C-terminal fragment containing the spacer 2 and four TSP type-1 domains.

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

Contains 1 PLAC domain.

Contains 8 TSP type-1 domains.

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Ontologies

Keywords

   Cellular componentExtracellular matrix
Secreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Glycoprotein
Phosphoprotein
Zymogen

Gene Ontology (GO)

None. [Check GOA]

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P58397-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P58397-2)

The sequence of this isoform differs from the canonical sequence as follows:
     212-229: DSVNISQKQELWREKWER → GIVTHMSSWVEESVLFFW
     230-1593: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 240215 By similarity
PRO_0000029186
Chain241 – 15931353A disintegrin and metalloproteinase with thrombospondin motifs 12
PRO_0000029187

Regions

Domain246 – 456211Peptidase M12B
Domain465 – 54480Disintegrin
Domain542 – 59756TSP type-1 1
Domain823 – 88260TSP type-1 2
Domain886 – 94257TSP type-1 3
Domain943 – 99654TSP type-1 4
Domain1312 – 136554TSP type-1 5
Domain1367 – 142155TSP type-1 6
Domain1422 – 147049TSP type-1 7
Domain1471 – 153161TSP type-1 8
Domain1534 – 157441PLAC
Region701 – 826126Spacer 1
Region996 – 1315320Spacer 2
Motif208 – 2136Cysteine switch By similarity
Compositional bias302 – 3054Poly-Glu
Compositional bias597 – 700104Cys-rich

Sites

Active site3931 By similarity
Metal binding2081Zinc; in inhibited form By similarity
Metal binding3921Zinc; catalytic By similarity
Metal binding3961Zinc; catalytic By similarity
Metal binding4021Zinc; catalytic By similarity

Amino acid modifications

Modified residue2341Phosphoserine
Modified residue2361Phosphoserine
Modified residue9811Phosphothreonine By similarity
Glycosylation1051N-linked (GlcNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation2151N-linked (GlcNAc...) Potential
Glycosylation4851N-linked (GlcNAc...) Potential
Glycosylation6851N-linked (GlcNAc...) Potential
Glycosylation7901N-linked (GlcNAc...) Potential
Glycosylation9511N-linked (GlcNAc...) Potential
Glycosylation11041N-linked (GlcNAc...) Potential
Glycosylation12751N-linked (GlcNAc...) Potential
Glycosylation13001N-linked (GlcNAc...) Potential
Glycosylation13201N-linked (GlcNAc...) Potential
Glycosylation13711N-linked (GlcNAc...) Potential
Glycosylation13781N-linked (GlcNAc...) Potential
Glycosylation15031N-linked (GlcNAc...) Potential
Disulfide bond370 ↔ 451 By similarity
Disulfide bond409 ↔ 435 By similarity
Disulfide bond554 ↔ 591 By similarity
Disulfide bond558 ↔ 596 By similarity
Disulfide bond569 ↔ 581 By similarity

Natural variations

Alternative sequence212 – 22918DSVNI…EKWER → GIVTHMSSWVEESVLFFW in isoform 2.
VSP_013141
Alternative sequence230 – 15931364Missing in isoform 2.
VSP_013142

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 16, 2001. Version 1.
Checksum: 07F9F48E63BD83A3

FASTA1,593177,545
        10         20         30         40         50         60 
MPCAQRSWLA NLSVVAQLLN FGALCYGRQP QPGPVRFPDR RQEHFIKGLP EYHVVGPVRV 

        70         80         90        100        110        120 
DASGHFLSYG LHYPITSSRR KRDLDGSEDW VYYRISHEEK DLFFNLTVNQ GFLSNSYIME 

       130        140        150        160        170        180 
KRYGNLSHVK MMASSAPLCH LSGTVLQQGT RVGTAALSAC HGLTGFFQLP HGDFFIEPVK 

       190        200        210        220        230        240 
KHPLVEGGYH PHIVYRRQKV PETKEPTCGL KDSVNISQKQ ELWREKWERH NLPSRSLSRR 

       250        260        270        280        290        300 
SISKERWVET LVVADTKMIE YHGSENVESY ILTIMNMVTG LFHNPSIGNA IHIVVVRLIL 

       310        320        330        340        350        360 
LEEEEQGLKI VHHAEKTLSS FCKWQKSINP KSDLNPVHHD VAVLLTRKDI CAGFNRPCET 

       370        380        390        400        410        420 
LGLSHLSGMC QPHRSCNINE DSGLPLAFTI AHELGHSFGI QHDGKENDCE PVGRHPYIMS 

       430        440        450        460        470        480 
RQLQYDPTPL TWSKCSEEYI TRFLDRGWGF CLDDIPKKKG LKSKVIAPGV IYDVHHQCQL 

       490        500        510        520        530        540 
QYGPNATFCQ EVENVCQTLW CSVKGFCRSK LDAAADGTQC GEKKWCMAGK CITVGKKPES 

       550        560        570        580        590        600 
IPGGWGRWSP WSHCSRTCGA GVQSAERLCN NPEPKFGGKY CTGERKRYRL CNVHPCRSEA 

       610        620        630        640        650        660 
PTFRQMQCSE FDTVPYKNEL YHWFPIFNPA HPCELYCRPI DGQFSEKMLD AVIDGTPCFE 

       670        680        690        700        710        720 
GGNSRNVCIN GICKMVGCDY EIDSNATEDR CGVCLGDGSS CQTVRKMFKQ KEGSGYVDIG 

       730        740        750        760        770        780 
LIPKGARDIR VMEIEGAGNF LAIRSEDPEK YYLNGGFIIQ WNGNYKLAGT VFQYDRKGDL 

       790        800        810        820        830        840 
EKLMATGPTN ESVWIQLLFQ VTNPGIKYEY TIQKDGLDND VEQMYFWQYG HWTECSVTCG 

       850        860        870        880        890        900 
TGIRRQTAHC IKKGRGMVKA TFCDPETQPN GRQKKCHEKA CPPRWWAGEW EACSATCGPH 

       910        920        930        940        950        960 
GEKKRTVLCI QTMVSDEQAL PPTDCQHLLK PKTLLSCNRD ILCPSDWTVG NWSECSVSCG 

       970        980        990       1000       1010       1020 
GGVRIRSVTC AKNHDEPCDV TRKPNSRALC GLQQCPSSRR VLKPNKGTIS NGKNPPTLKP 

      1030       1040       1050       1060       1070       1080 
VPPPTSRPRM LTTPTGPESM STSTPAISSP SPTTASKEGD LGGKQWQDSS TQPELSSRYL 

      1090       1100       1110       1120       1130       1140 
ISTGSTSQPI LTSQSLSIQP SEENVSSSDT GPTSEGGLVA TTTSGSGLSS SRNPITWPVT 

      1150       1160       1170       1180       1190       1200 
PFYNTLTKGP EMEIHSGSGE EREQPEDKDE SNPVIWTKIR VPGNDAPVES TEMPLAPPLT 

      1210       1220       1230       1240       1250       1260 
PDLSRESWWP PFSTVMEGLL PSQRPTTSET GTPRVEGMVT EKPANTLLPL GGDHQPEPSG 

      1270       1280       1290       1300       1310       1320 
KTANRNHLKL PNNMNQTKSS EPVLTEEDAT SLITEGFLLN ASNYKQLTNG HGSAHWIVGN 

      1330       1340       1350       1360       1370       1380 
WSECSTTCGL GAYWKRVECT TQMDSDCAAI QRPDPAKRCH LRPCAGWKVG NWSKCSRNCS 

      1390       1400       1410       1420       1430       1440 
GGFKIREIQC VDSRDHRNLR PFHCQFLAGI PPPLSMSCNP EPCEAWQVEP WSQCSRSCGG 

      1450       1460       1470       1480       1490       1500 
GVQERGVFCP GGLCDWTKRP TSTMSCNEHL CCHWATGNWD LCSTSCGGGF QKRIVQCVPS 

      1510       1520       1530       1540       1550       1560 
EGNKTEDQDQ CLCDHKPRPP EFKKCNQQAC KKSADLLCTK DKLSASFCQT LKAMKKCSVP 

      1570       1580       1590 
TVRAECCFSC PQTHITHTQR QRRQRLLQKS KEL

« Hide

Isoform 2 [UniParc].

Checksum: 11FBCB40E82091F6
Show »

22926,003

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References

« Hide 'large scale' references
[1]"Identification, characterization, and intracellular processing of ADAM-TS12, a novel human disintegrin with a complex structural organization involving multiple thrombospondin-1 repeats."
Cal S., Argueelles J.M., Fernandez P.L., Lopez-Otin C.
J. Biol. Chem. 276:17932-17940(2001) [PubMed: 11279086] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal lung.
[2]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-234 AND SER-236, MASS SPECTROMETRY.
Tissue: Epithelium.
+Additional computationally mapped references.

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Cross-references

Sequence databases

AJ250725 mRNA. Translation: CAC20419.1.
AY358745 mRNA. Translation: AAQ89105.1.
BC058841 mRNA. Translation: AAH58841.1.
RefSeqNP_112217.2.
UniGeneHs.12680

3D structure databases

HSSPHSSP built from PDB template 1LSL based on UniProtKB P07996.
ModBaseSearch...

Protein family/group databases

MEROPSM12.237.

PTM databases

PhosphoSiteP58397.

Genome annotation databases

EnsemblENSG00000151388. Homo sapiens. [Contig view]
GeneID81792.
KEGGhsa:81792.

Organism-specific databases

H-InvDBHIX0032007.
HGNCHGNC:14605. ADAMTS12.
MIM606184. gene.
PharmGKBPA24538.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP58397.
HOVERGENP58397.

Gene expression databases

ArrayExpressP58397.
CleanExHS_ADAMTS12.
GermOnlineENSG00000151388. Homo sapiens.

Family and domain databases

InterProIPR010294. ADAM_spacer1.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR001818. Pept_M10A_M12B.
IPR006025. Pept_M_Zn_BS.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR010909. PLAC.
IPR000884. TSP1.
IPR008085. TSP_1.
[Graphical view]
PfamPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 6 hits.
[Graphical view]
PRINTSPR01857. ADAMTSFAMILY.
PR01705. TSP1REPEAT.
SMARTSM00209. TSP1. 8 hits.
[Graphical view]
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS00546. CYSTEINE_SWITCH. False negative.
PS00427. DISINTEGRIN_1. False negative.
PS50214. DISINTEGRIN_2. False negative.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 6 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
BLOCKSSearch...
ProtoNetSearch...

Other Resources

NextBio72100.
SOURCESearch...

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Entry information

Entry nameATS12_HUMAN
AccessionPrimary (citable) accession number: P58397
Secondary accession number(s): Q6UWL3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: November 16, 2001
Last modified: November 4, 2008
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Peptidase families

Classification of peptidase families and list of entries

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents